Reaktion #1865235

ord-efba41be51f248e49525aed90bbb269e

Lösungsmittel

Reaktionsbedingungen

Temperatur
-65°CELSIUS
Detaillierte Bedingungen
See reaction.notes.procedure_details.

Aufarbeitung

  1. 1
    SonstigeThe reaction mixture was quenched with saturated aqueous NH4Cl
  2. 2
    workup.ADDITIONdiluted with ethyl acetate and water
  3. 3
    SonstigeLayers were separated
  4. 4
    Extraktionthe aqueous layer was extracted with ethyl acetate
  5. 5
    WaschenThe combined organic layers were washed with brine
  6. 6
    Sonstigedried
  7. 7
    Filtrationfiltered
  8. 8
    Sonstigeevaporated
  9. 9
    SonstigeThe crude product was purified by silica gel column chromatography
  10. 10
    Wascheneluting with a gradient of MeOH (2-3%) in DCM
  11. 11
    workup.ADDITIONProduct containing fractions
  12. 12
    Sonstigeevaporated
  13. 13
    Sonstigedried

Vorschrift

A solution of LHMDS (1M in THF, 260 μL, 0.260 mmol) was added to suspension of phenyl 7-(dimethoxymethyl)-6-(1H-imidazol-1-yl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylate (intermediate 320, 49.7 mg, 0.126 mmol) and 6-amino-4-((2-methoxyethyl)amino)nicotinonitrile (intermediate 75, 25 mg, 0.130 mmol) in THF (1 ml) at −70° C. and the reaction mixture was stirred at −65° C. for 90 min. The reaction mixture was quenched with saturated aqueous NH4Cl and diluted with ethyl acetate and water. Layers were separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine, dried using Na2SO4, filtered and evaporated. The crude product was purified by silica gel column chromatography eluting with a gradient of MeOH (2-3%) in DCM. Product containing fractions were combined, evaporated and dried to yield the title compound as a white solid. (UPLC-MS 3) tR 0.79 min; ESI-MS 493.1 [M+H]+.

Quelle

DOI: 10.6084/m9.figshare.5104873.v1Patent: US09266883B2uspto-grants-2016_02